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Background: Multiple Sclerosis (MS) is an autoimmune disease associated with physical disability, psychological impairment, and cognitive dysfunctions. Consequently, the disease burden is substantial, and treatment choices are limited. In this randomized, double-blind study, we conducted repeated prefrontal electrical stimulation in 40 patients with MS to evaluate mental health variables (quality of life, sleep difficulties, psychological distress) and cognitive dysfunctions (psychomotor speed, working memory, attention/vigilance), marking it as the third largest sample size tDCS research conducted in MS to date., Methods: The patients were randomly assigned (block randomization method) to two groups of sham (n = 20), or 1.5-mA (n = 20) transcranial direct current stimulation (tDCS) targeting the left dorsolateral prefrontal cortex (F3) and right frontopolar cortex (Fp2) with anodal and cathodal stimulation respectively (electrode size: 25 cm 2 ). The treatment included 10 sessions of 20 min of stimulation delivered every other day. Outcome measures were MS quality of life, sleep quality, psychological distress, and performance on a neuropsychological test battery dedicated to cognitive dysfunctions in MS (psychomotor speed, working memory, and attention). All outcome measures were evaluated at the pre-intervention and post-intervention assessments. Both patients and technicians delivering the stimulation were unaware of the type of stimulation being used., Results: Repeated prefrontal real tDCS significantly improved quality of life and reduced sleep difficulties and psychological distress compared to the sham group. It, furthermore, improved psychomotor speed, attention, and vigilance compared to the sham protocol. Improvement in mental health outcome variables and cognitive outperformance were interrelated and could predict each other., Conclusions: Repeated prefrontal and frontopolar tDCS ameliorates secondary clinical symptoms related to mental health and results in beneficial cognitive effects in patients with MS. These results support applying prefrontal tDCS in larger trials for improving mental health and cognitive dysfunctions in MS., Trial Registration: ClinicalTrials.gov Identifier: NCT06401928., (© 2024. The Author(s).)

Background: Ending a romantic relationship is one of the most painful losses an adult experience. Neuroimaging studies suggest that there is a neuropsychological link between breakup experiences and bereaved individuals, and that specific prefrontal regions are involved. The aim of this study was to determine whether enhancement of left DLPFC and right VLPFC activity with a novel intensified anodal transcranial direct current stimulation protocol reduces core symptoms of love trauma syndrome (LTS) and improves treatment-related variables., Methods: In this randomized, sham-controlled, single-blind parallel trial, we assessed the efficacy of an intensified anodal stimulation protocol (20 min, twice-daily sessions with 20 min intervals, 5 consecutive days) with two montages (left DLPFC vs right VLPFC) to reduce love trauma symptoms. 36 participants with love trauma syndrome were randomized in three tDCS condition (left DLPFC, right VLPFC, sham stimulation). LTS symptoms, treatment-related outcome variables (depressive state, anxiety, emotion regulation, positive and negative affect), and cognitive functions were assessed before, right after, and one month after intervention., Results: Both DLPFC and VLPFC protocols significantly reduced LTS symptoms, and improved depressive state and anxiety after the intervention, as compared to the sham group. The improving effect of the DLPFC protocol on love trauma syndrome was significantly larger than that of the VLPFC protocol. For emotion regulation and positive and negative affect, improved regulation of emotions and positive affect and reduced negative affect were revealed after intervention in the two real stimulation conditions compared to the sham. For cognitive functions, no significant difference was observed between the groups, but again a positive effect of intervention within groups in the real stimulation conditions (DLPFC and VLPFC) was found for most components of the cognitive tasks., Conclusions: Enhancement of left DLPFC and right VLPFC activity with intensified stimulation improves LTS symptoms and treatment-related variables. For LTS symptoms, DLPFC stimulation was more efficient than VLPFC stimulation., For the other variables, no significant difference was observed between these two stimulation groups. These promising results require replication in larger trials., Competing Interests: Declaration of competing interest None., (Copyright © 2024. Published by Elsevier Ltd.)

Introduction: Fear extinction is a fundamental component of exposure-based therapies for anxiety-related disorders. The renewal of fear in a different context after extinction highlights the importance of contextual factors. In this study, we aimed to investigate the causal role of the left inferior frontal gyrus (LiFG) in the context-dependency of fear extinction learning via administration of transcranial direct current stimulation (tDCS) over this area., Methods: 180 healthy subjects were assigned to 9 groups: 3 tDCS conditions (anodal, cathodal, and sham) × 3 context combinations (AAA, ABA, and ABB). The fear conditioning/extinction task was conducted over three consecutive days: acquisition, extinction learning, and extinction recall. tDCS (2 mA, 10min) was administered during the extinction learning phase over the LiFG via a 4-electrode montage. Skin conductance response (SCR) data and self-report assessments were collected., Results: During the extinction learning phase, groups with excitability-enhancing anodal tDCS showed a significantly higher fear response to the threat cues compared to cathodal and sham stimulation conditions, irrespective of contextual factors. This effect was stable until the extinction recall phase. Additionally, excitability-reducing cathodal tDCS caused a significant decrease of the response difference between the threat and safety cues during the extinction recall phase. The self-report assessments showed no significant differences between the conditions throughout the experiment., Conclusion: Independent of the context, excitability enhancement of the LiFG did impair fear extinction, and led to preservation of fear memory. In contrast, excitability reduction of this area enhanced fear extinction retention. These findings imply that the LiFG plays a role in the fear extinction network, which seems to be however context-independent., Competing Interests: Declaration of competing interest MA Nitsche is a member of Scientific Advisory Boards of Neuroelectrics and Precisis. None of the remaining authors have potential conflicts of interest to be disclosed., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background and Aims: Mind wandering refers to spontaneously occurring, often disruptive thoughts during an ongoing task or resting state. The ventromedial prefrontal cortex (vmPFC) and dorsolateral prefrontal cortex (dlPFC) are two main cortical areas which are involved in this process. This study aimed to explore the interaction of these areas during mind wandering by enhancing specific oscillatory activity of these areas via transcranial alternating current stimulation (tACS) in the theta frequency range., Material and Methods: Eighteen healthy adults participated in a randomized, single-blinded, crossover study. tACS (1.5 mA, 6 Hz) was applied in five sessions with one week interval via (1) two channels with synchronized stimulation over the left dlPFC and right vmPFC, (2) the same electrode placement with anti-phase stimulation, (3) stimulation over the left dlPFC only, (4) stimulation over right vmPFC only, and (5) sham stimulation. The return electrodes were placed over the contralateral shoulder in all conditions. The sustained attention to response task (SART) with embedded probes about task-unrelated-thoughts and awareness of these thoughts was performed during intervention., Results: Stimulation did not alter SART performance. Right vmPFC stimulation decreased mind wandering and increased awareness of mind wandering. Left dlPFC stimulation and desynchronized stimulation over the dlPFC and vmPFC increased mind wandering compared to the sham stimulation condition. Synchronized stimulation had no effect on mind wandering, but increased awareness of mind wandering., Conclusion: The results suggest that regional entrainment of the vmPFC decreases mind wandering and increases awareness of mind wandering, whereas regional entrainment of the dlPFC increases mind wandering, but decreases awareness. Under desynchronized stimulation of both areas, the propensity of mind wandering was increased, whereas synchronized stimulation increased the awareness of mind wandering. These results suggest a role of the dlPFC in initiation of mind wandering, whereas the vmPFC downregulates mind wandering, and might exert this function by counteracting respective dlPFC effects via theta oscillations., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Transcranial direct current stimulation (tDCS) applied over the prefrontal cortex has been shown to improve behavioral responsiveness in patients with disorders of consciousness following severe brain injury, especially those in minimally conscious state (MCS). However, one potential barrier of clinical response to tDCS is the timing of stimulation with regard to the fluctuations of vigilance that characterize this population. Indeed, a previous study showed that the vigilance of MCS patients has periodic average cycles of 70 min (range 57-80 min), potentially preventing them to be in an optimal neural state to benefit from tDCS when applied randomly. To tackle this issue, we propose a new protocol to optimize the application of tDCS by selectively stimulating at high and low vigilance states. Electroencephalography (EEG) real-time spectral entropy will be used as a marker of vigilance and to trigger tDCS, in a closed-loop fashion. We will conduct a randomized controlled crossover clinical trial on 16 patients in prolonged MCS who will undergo three EEG-tDCS sessions 5 days apart (1. tDCS applied at high vigilance; 2. tDCS applied at low vigilance; 3. tDCS applied at a random moment). Behavioral effects will be assessed using the Coma Recovery Scale-Revised at baseline and right after the stimulations. EEG will be recorded throughout the session and for 30 min after the end of the stimulation. This unique and novel approach will provide patients' tailored treatment options, currently lacking in the field of disorders of consciousness., (Copyright © 2021 Elsevier B.V. All rights reserved.)

The ventromedial and dorsolateral prefrontal cortex are two major prefrontal regions that usually interact in serving different cognitive functions. On the other hand, these regions are also involved in cognitive processing of emotions but their contribution to emotional processing is not well-studied. In the present study, we investigated the role of these regions in three dimensions (valence, arousal and dominance) of emotional processing of stimuli via ratings of visual stimuli performed by the study participants on these dimensions. Twenty- two healthy adult participants (mean age 25.21 ± 3.84 years) were recruited and received anodal and sham transcranial direct current stimulation (tDCS) (1.5 mA, 15 min) over the dorsolateral prefrontal cortex (dlPFC) and and ventromedial prefrontal cortex (vmPFC) in three separate sessions with an at least 72-h interval. During stimulation, participants underwent an emotional task in each stimulation condition. The task included 100 visual stimuli and participants were asked to rate them with respect to valence, arousal, and dominance. Results show a significant effect of stimulation condition on different aspects of emotional processing. Specifically, anodal tDCS over the dlPFC significantly reduced valence attribution for positive pictures. In contrast, anodal tDCS over the vmPFC significantly reduced arousal ratings. Dominance ratings were not affected by the intervention. Our results suggest that the dlPFC is involved in control and regulation of valence of emotional experiences, while the vmPFC might be involved in the extinction of arousal caused by emotional stimuli. Our findings implicate dimension-specific processing of emotions by different prefrontal areas which has implications for disorders characterized by emotional disturbances such as anxiety or mood disorders.

Background: Cognitive control (CC) is an important prerequisite for goal-directed behaviour and efficient information processing. Impaired CC is associated with reduced prefrontal cortex activity and various mental disorders, but may be effectively tackled by transcranial direct current stimulation (tDCS)-enhanced training. However, study data are inconsistent as efficacy depends on stimulation parameters whose implementations vary widely between studies., Objective: We systematically tested various tDCS parameter effects (anodal/cathodal polarity, 1/2 mA stimulation intensity, left/right prefrontal cortex hemisphere) on a six-session CC training combined with tDCS., Methods: Nine groups of healthy humans (male/female) received either anodal/cathodal tDCS of 1/2 mA over the left/right PFC or sham stimulation, simultaneously with a CC training (modified adaptive Paced Auditory Serial Addition Task [PASAT]). Subjects trained thrice per week (19 min each) for two weeks. We assessed performance progress in the PASAT before, during, and after training. Using a hierarchical approach, we incrementally narrowed down on optimal stimulation parameters supporting CC. Long-term CC effects as well as transfer effects in a flanker task were assessed after the training period as well as three months later., Results: Compared to sham stimulation, anodal but not cathodal tDCS improved performance gains. This was only valid for 1 mA stimulation intensity and particularly detected when applied to the left PFC., Conclusions: Our results confirm beneficial, non-linear effects of anodal tDCS on cognitive training in a large sample of healthy subjects. The data consolidate the basis for further development of functionally targeted tDCS, supporting cognitive control training in mental disorders and guiding further development of clinical interventions., Competing Interests: Declaration of competing interest SW and CP declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. MAN is scientific advisor for Neuroelectrics, and NeuroDevice., (Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Creativity is the use of original ideas to accomplish something innovative. Previous research supports the notion that creativity is facilitated by an activation of the right and/or a deactivation of the left prefrontal cortex. In contrast, recent brain imaging studies suggest that creativity improves with left frontal activation., Objective: The present study was designed to further elucidate the neural basis of and ways to modulate creativity, based on the modulation of prefrontal cortical activity through the non-invasive brain stimulation technique transcranial direct current stimulation (tDCS)., Methods: Ninety healthy University students performed three tasks on major aspects of creativity: conceptual expansion (Alternate Uses Task, AUT), associative thinking (Compound Remote Associate Task, CRA), and set shifting ability (Wisconsin Card Sorting Task, WCST). Simultaneously, they received cathodal stimulation of the left and anodal stimulation of the right inferior frontal gyrus (IFG), the reverse protocol, or sham stimulation., Results: The main pattern of results was a superior performance with bilateral left cathodal/right anodal stimulation, and an inferior performance in the reversed protocol compared to sham stimulation. As a potential underlying physiological mechanism, resting state EEG beta power, indicative of enhanced cortical activity, in the right frontal area increased with anodal stimulation and was associated with better performance., Conclusion: The findings provide new insights into ways of modulating creativity, whereby a deactivation of the left and an activation of the right prefrontal cortex with tDCS is associated with increased creativity. Potential future applications might include tDCS for patients with mental disorders and for healthy individuals in creative professions., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Accounts of cognitive processes in judgment and decision-making are frequently based on a dual-process framework, which reflects two qualitatively different types of processing: intuitive (Type 1) and analytical (Type 2) processes., Objective: The present study investigated the effects of bilateral transcranial direct current stimulation (tDCS) to the dorsolateral prefrontal cortex (DLPFC) on judgment and decision-making performance., Methods: Participants received anodal tDCS stimulation to the right DLPFC, left DLPFC or sham. There were 3 tasks: vignettes measuring heuristic thinking, belief bias syllogisms, and the cognitive reflection test (CRT), a measure of the ability to inhibit automatic responses to reach a correct solution. Fifty-four participants (mean age = 24.63 ± 4.46 years; 29 females) were recruited., Results: Results showed that anodal tDCS to the right DLPFC was associated with an increase in cognitive reflection performance (Type 2 processing) as compared to left DLPFC and to sham. Logic thinking was reduced following anodal tDCS to the left DLPFC., Conclusion: These findings are broadly consistent with a dual process framework, and cannot be explained by differences in cognitive ability and thinking style. The results demonstrate the involvement of the right DLPFC in cognitive reflection, and suggest the possibility of improving cognitive performance through tDCS., (Crown Copyright © 2018. Published by Elsevier Inc. All rights reserved.)

Reduced activity of the frontal lobes, and particularly of the prefrontal cortex, has been related with violent behavior, aggression and crime. The causal importance of prefrontal cortex activity for aggressive behaviors and the self-perception of aggressiveness needs however to be clarified. The aim of this study was to explore the effect of an anodal transcranial direct current stimulation protocol (tDCS, 1.5 mA, 15 min), which, according to previous studies, enhances cortical excitability, applied bilaterally over the prefrontal cortex on self-reported aggressiveness. Two imprisoned violent offender cohorts, discerned by the degree of aggressiveness (murderers vs. non-murderers), were included in this single-blind sham-controlled study. Self-reported aggressiveness was recorded before and after 3 tDCS sessions (one session per day). Four dimensions of aggression were evaluated by means of the standardized Buss-Perry Aggression Questionnaire (BAQ). In both inmate groups the results revealed an aggression-reducing effect of tDCS on the Physical aggression, Anger, and Verbal aggression dimensions of the BAQ. In the Hostility dimension, tDCS significantly reduced aggression only in the group of murderers. These results suggest that modulation of prefrontal cortex excitability by 3 consecutive sessions of tDCS reduces self-reported aggressiveness similarly in murderer and non-murderer samples., (Copyright © 2018 IBRO. Published by Elsevier Ltd. All rights reserved.)

Background: Transcranial direct current stimulation (tDCS) is an increasingly popular method of modulating cognitive functions in humans. However, some doubt its efficacy as findings are inconsistent or remain unreplicated. It is speculated dopamine (DA) might play an important role in this inconsistency, by determining the direction and strength of the cognitive-behavioral effects of tDCS. However, so far evidence for this hypothesis has been correlational in nature, precluding definitive conclusions., Objective: The present proof-of-principle study aimed at investigating a potentially causal role for DA in the effect of tDCS on cognition in healthy humans., Methods: In Experiment 1 we aimed to replicate previous findings showing administration of DA's precursor l-Tyrosine (Tyr), presumably by inducing a modest increase in DA level, can enhance working memory (WM) performance as assessed with a verbal N-back task. In Experiment 2 we investigated the effect of Tyr administration on bilateral tDCS over dorsolateral prefrontal cortex (DLPFC) and WM., Results: Experiment 1 showed Tyr administration enhances performance in a verbal N-back task. Experiment 2 showed Tyr modulates the effect of bilateral tDCS over DLPFC on WM. Specifically, tDCS had opposite effects on performance depending on current direction through the brain and Tyr administration., Conclusions: The present study provides two major findings. First, we replicate Tyr's beneficial effect on verbal WM. Second, our results indicate a causal role for DA in the effect of tDCS on cognition. For this reason, we encourage future studies to consider the modulating effect of DA, as a step towards more consistent and replicable results regarding the efficacy of tDCS., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Background: Social categorization and group identification are essential ingredients for maintaining a positive self-image that often lead to negative, implicit stereotypes toward members of an out-group. The medial prefrontal cortex (mPFC) may be a critical component in counteracting stereotypes activation., Objective: Here, we assessed the causal role of the mPFC in these processes by non-invasive brain stimulation via transcranial direct current stimulation (tDCS)., Method: Participants (n = 60) were randomly and equally assigned to receive anodal, cathodal, or sham stimulation over the mPFC while performing an Implicit Association Test (IAT): They were instructed to categorize in-group and out-group names and positive and negative attributes., Results: Anodal excitability-enhancing stimulation decreased implicit biased attitudes toward out-group members compared to excitability-diminishing cathodal and sham stimulation., Conclusions: These results provide evidence for a critical role of the mPFC in counteracting stereotypes activation. Furthermore, our results are consistent with previous findings showing that increasing cognitive control may overcome negative bias toward members of social out-groups., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Background: Transcranial direct current stimulation over the dorsolateral prefrontal cortex has been shown to be clinically useful in the treatment of drug addiction., Methods: We conducted a double-blind randomized clinical trial aiming to assess the effects of bilateral dorsolateral prefrontal cortex transcranial direct current stimulation (left cathodal/right anodal) on crack-cocaine addiction. We defined craving as the primary outcome, and other clinical measurements, including depressive and anxiety symptoms, and quality of life, as secondary outcomes. Seventeen male crack-cocaine users (mean age 30.4 ± 9.8 SD) were randomized to receive 5 sessions of active transcranial direct current stimulation (2 mA, 35 cm(2), for 20 minutes), every other day, and 19 males (mean age 30.3 ± 8.4 SD) to receive sham-transcranial direct current stimulation (placebo) as control group., Results: Craving scores were significantly reduced in the transcranial direct current stimulation group after treatment when compared with sham-transcranial direct current stimulation (P = .028) and baseline values (P = .003), and decreased linearly over 4 weeks (before, during, and after treatment) in the transcranial direct current stimulation group only (P = .047). Changes of anxiety scores towards increase in the sham-transcranial direct current stimulation and decrease in the transcranial direct current stimulation group (P = .03), and of the overall perception of quality of life (P = .031) and of health (P = .048) towards decrease in the sham-transcranial direct current stimulation group and increase in the transcranial direct current stimulation group differed significantly between groups., Conclusions: Repetitive bilateral transcranial direct current stimulation over the dorsolateral prefrontal cortex reduced craving for crack-cocaine use, decreased anxiety, and improved quality of life. We hypothesize that transcranial direct current stimulation effects may be associated with increased prefrontal processing and regulation of craving behavior., (© The Author 2015. Published by Oxford University Press on behalf of CINP.)

The prefrontal cortex is involved in a multitude of cognitive, emotional, motivational, and social processes, so exploring its specific functions is crucial for understanding human experience and behavior. Functional imaging approaches have largely contributed to the enhancement of our understanding, but might have limitations in establishing causal relationships between physiology and the related psychological and behavioral processes. Non-invasive electrical stimulation with direct or alternating currents can help to enhance our understanding with regard to specific processes, and might provide future protocols able to improve them in case of malfunctions. We review the current state of the field, and provide an outlook for future developments.

Preliminary small studies have shown that transcranial direct current stimulation (tDCS) reduces craving in alcoholic subjects. It is unclear whether tDCS also leads to changes in clinically meaningful outcomes for alcohol dependence in a properly powered phase II randomized clinical trial. We aimed to investigate whether repetitive tDCS changes the risk of alcohol use relapse in severe alcoholics from outpatient services. Thirty-five subjects were randomized to receive active bilateral [left cathodal/right anodal over the dorsolateral prefrontal cortex (dlPFC)] repetitive (five consecutive days) tDCS (2 mA, 35 cm2, two times daily stimulation for 13 min with a 20-min interval) or sham-tDCS. There were two dropouts before treatment. From 33 alcoholic subjects, 17 (mean age 45.5±8.9 s.d., 16 males) were randomized to sham and 16 (44±7.8 s.d., 16 males) to real tDCS treatment. By the end of the six months of follow-up, two subjects treated with sham (11.8%) and eight treated with real tDCS (50%) were still alcohol-abstinent [p=0.02, Long-rank (Mantel-Cox) Test, HR=0.35 (95% CI, 0.14-0.85)]. No differences with regard to changes on scores of craving, frontal function, global mental status, depressive or anxiety symptoms were observed between groups. However, subjects from the tDCS group improved with regard to their overall perception of quality of life (p=0.02), and increased their scores in the environment domain (p=0.04) after treatment. Bilateral tDCS over dlPFC reduces relapse probability in severe alcoholic subjects and results in improved perception of quality of life.

Targeting memory processes by noninvasive interventions is a potential gateway to modulate fear memories as shown by animal and human studies in recent years. Modulation of fear memories by noninvasive brain stimulation techniques might be an attractive approach, which, however, has not been examined so far. We investigated the effect of transcranial direct current stimulation (tDCS) applied to the right dorsolateral prefrontal cortex and left supraorbital region on fear memories in humans. Seventy-four young, healthy individuals were assigned randomly to two groups, which underwent fear conditioning with mild electric stimuli paired with a visual stimulus. Twenty-four hours later, both groups were shown a reminder of the conditioned fearful stimulus. Shortly thereafter, they received either tDCS (right prefrontal--anodal, left supraorbital--cathodal) for 20 min at 1 mA current intensity or sham stimulation. A day later, fear responses of both groups were compared by monitoring skin conductance. On day 3, during fear response assessment, the tDCS group had a significantly (P<0.05) higher mean skin conductance in comparison with the sham group. These results suggest that tDCS (right prefrontal--anodal, left supraorbital--cathodal) enhanced fear memories, possibly by influencing the prefrontal cortex-amygdala circuit underlying the memory for fear.

Transcranial Direct Current Stimulation (tDCS) has been shown to reduce acute substance craving in drug addicts, and improve cognition in neuropsychiatric patients. Here we aimed to explore further tDCS induced behavioral and neurophysiological modulation including assessment of relapse rate over a prolonged time course in alcoholism. We examined the effects of repeated anodal tDCS (2mA, 35 cm(2), 20min) over the left dorsolateral prefrontal cortex (DLPFC) on relapse to the use of alcohol in alcoholics from outpatient services, who received additional routine clinical treatment. Furthermore, event related potentials (ERPs), cognitive and frontal executive processes, craving, depressive and anxiety symptoms were obtained before and after treatment. From thirteen alcoholic subjects, seven were randomized to sham-tDCS and six to real tDCS treatment (once a week for five consecutive weeks). Depressive symptoms and craving were reduced to a larger extent in the tDCS group compared to the sham group (p=0.005 and p=0.015, respectively). On the other hand, active tDCS was able to block the increase in neural activation triggered by alcohol related and neutral cues in prefrontal cortex (PFC) as indexed by ERP as seen in the sham-tDCS group. Finally, there was a trend for increased change in executive function in the tDCS group compared to the sham-tDCS group (p=0.082), and, similarly, a trend for more relapses in the tDCS group compared to sham tDCS (four alcoholic subjects (66.7%) vs. one (14.3%), p=0.053).These results confirm the previous findings of tDCS effects on craving in alcoholism and also extend these findings as we showed also tDCS-related mood improvement. However, potential increase in relapse is possible; thus the clinical value of an increase in craving and improvement in depression and executive function needs to be carefully assessed in further studies; including investigation of optimal parameters of stimulation., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Functional cortical circuits for central executive functions have been shown to emerge by theta (~6 Hz) phase-coupling of distant cortical areas. It has been repeatedly shown that frontoparietal theta coupling at ~0° relative phase is associated with recognition, encoding, short-term retention, and planning; however, a causal link has not been demonstrated so far. Here we used transcranial alternating current stimulation simultaneously applied at 6 Hz over left prefrontal and parietal cortices with a relative 0° ("synchronized" condition) or 180° ("desynchronized" condition) phase difference or a placebo stimulation condition, whereas healthy subjects performed a delayed letter discrimination task. We show that exogenously induced frontoparietal theta synchronization significantly improves visual memory-matching reaction times as compared to placebo stimulation. In contrast, exogenously induced frontoparietal theta desynchronization deteriorates performance. The present findings provide for the first time evidence of causality of theta phase-coupling of distant cortical areas for cognitive performance in healthy humans. Moreover, the results demonstrate the suitability of transcranial alternating current stimulation to artificially induce coupling or decoupling of behaviorally relevant brain rhythms between segregated cortical regions., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

The temporal maintenance and subsequent retrieval of information that no longer exists in the environment is called working memory. It is believed that this type of memory is controlled by the persistent activity of neuronal populations, including the prefrontal, temporal, and parietal cortex. For a long time, it has been controversially discussed whether, in working memory, the PFC stores past sensory events or, instead, its activation is an extramnemonic source of top-down control over posterior regions. Recent animal studies suggest that specific information about the contents of working memory can be decoded from population activity in prefrontal areas. However, it has not been shown whether the contents of working memory during the delay periods can be decoded from EEG recordings in the human brain. We show that by analyzing the nonlinear dynamics of EEG oscillatory patterns it is possible to noninvasively decode with high accuracy, during encoding and maintenance periods, the contents of visual working memory information within high-gamma oscillations in the human PFC. These results are thus in favor of an active storage function of the human PFC in working memory; this, without ruling out the role of PFC in top-down processes. The ability to noninvasively decode the contents of working memory is promising in applications such as brain computer interfaces, together with computation of value function during planning and decision making processes.

We aimed to assess whether modulation of the dorsolateral prefrontal cortex (DLFPC) with noninvasive brain stimulation, namely transcranial direct current stimulation (tDCS), modifies food craving in healthy subjects. We performed a randomized sham-controlled cross-over study in which 23 subjects received sham and active tDCS (anode left/cathode right and anode right/cathode left) of the DLPFC. Subjects were exposed to food and also watched a movie of food associated with strong craving. Desire for food consumption was evaluated by visual analogue scales (VAS) and food consumption before and after treatment. In addition we measured visual attention to food using an eye tracking system. Craving for viewed foods as indexed by VAS was reduced by anode right/cathode left tDCS. After sham stimulation, exposure to real food or food-related movie increased craving; whereas after anode left/cathode right tDCS, the food-related stimuli did not increase craving levels, as revealed by the VAS scale. Moreover, compared with sham stimulation, subjects fixated food-related pictures less frequently after anode right/cathode left tDCS and consumed less food after both active stimulation conditions. These changes were not related to mood changes after any type of tDCS treatment. The effects of tDCS on food craving might be related to a modulation of neural circuits associated with reward and decision-making.

Preliminary findings suggest that transcranial direct current stimulation (tDCS) can have antidepressant effects. We sought to test this further in a parallel-group, double-blind clinical trial with 40 patients with major depression, medication-free randomized into three groups of treatment: anodal tDCS of the left dorsolateral prefrontal cortex (active group - 'DLPFC'); anodal tDCS of the occipital cortex (active control group - 'occipital') and sham tDCS (placebo control group - 'sham'). tDCS was applied for 10 sessions during a 2-wk period. Mood was evaluated by a blinded rater using the Hamilton Depression Rating Scale (HDRS) and Beck Depression Inventory (BDI). The treatment was well tolerated with minimal side-effects that were distributed equally across all treatment groups. We found significantly larger reductions in depression scores after DLPFC tDCS [HDRS reduction of 40.4% (+/-25.8%)] compared to occipital [HDRS reduction of 21.3% (+/-12.9%)] and sham tDCS [HDRS reduction of 10.4% (+/-36.6%)]. The beneficial effects of tDCS in the DLPFC group persisted for 1 month after the end of treatment. Our findings support further investigation on the effects of this novel potential therapeutic approach - tDCS - for the treatment of major depression.

Objective: Because neuroimaging studies have shown that cue-provoked smoking craving is associated with changes in the activity of the bilateral dorsolateral prefrontal cortex (DLPFC), we aimed to investigate whether a powerful technique of noninvasive brain stimulation, transcranial direct current stimulation (tDCS), reduces cue-provoked smoking craving as indexed by a visual analog scale., Method: We performed a randomized, sham-controlled crossover study in which 24 subjects received sham and active tDCS (anodal tDCS of the left and right DLPFC) in a randomized order. Craving was induced by cigarette manipulation and exposure to a smoking video. The study ran from January 2006 to October 2006., Results: Smoking craving was significantly increased after exposure to smoking-craving cues (p < .0001). Stimulation of both left and right DLPFC with active, but not sham, tDCS reduced craving significantly when comparing craving at baseline and after stimulation, without (p = .007) and with (p = .005) smoking-craving cues. There were no significant mood changes in any of the conditions of stimulation. Adverse events were mild and distributed equally across all treatment conditions., Conclusions: Our findings extend the results of a previous study on the use of brain stimulation to reduce craving, showing that cortical stimulation with tDCS is beneficial for reducing cue-provoked craving, and thus support the further exploration of this technique for smoking cessation.

Electrical stimulation of deep brain structures, such as globus pallidus and subthalamic nucleus, is widely accepted as a therapeutic tool for patients with Parkinson's disease (PD). Cortical stimulation either with epidural implanted electrodes or repetitive transcranial magnetic stimulation can be associated with motor function enhancement in PD. We aimed to study the effects of another noninvasive technique of cortical brain stimulation, transcranial direct current stimulation (tDCS), on motor function and motor-evoked potential (MEP) characteristics of PD patients. We tested tDCS using different electrode montages [anodal stimulation of primary motor cortex (M1), cathodal stimulation of M1, anodal stimulation of dorsolateral prefrontal cortex (DLPFC), and sham-stimulation] and evaluated the effects on motor function--as indexed by Unified Parkinson's Disease Rating Scale (UPDRS), simple reaction time (sRT) and Purdue Pegboard test--and on corticospinal motor excitability (MEP characteristics). All experiments were performed in a double-blinded manner. Anodal stimulation of M1 was associated with a significant improvement of motor function compared to sham-stimulation in the UPDRS (P < 0.001) and sRT (P = 0.019). This effect was not observed for cathodal stimulation of M1 or anodal stimulation of DLPFC. Furthermore, whereas anodal stimulation of M1 significantly increased MEP amplitude and area, cathodal stimulation of M1 significantly decreased them. There was a trend toward a significant correlation between motor function improvement after M1 anodal-tDCS and MEP area increase. These results confirm and extend the notion that cortical brain stimulation might improve motor function in patients with PD.

The aim of our study was to test if the electrical stimulation of the prefrontal cortex (PFC) could modify probabilistic classification learning (PCL). Transcranial direct current stimulation (tDCS) was administered to the left prefrontal and to the primary visual cortex of 22 healthy subjects while they performed a PCL task. In this task subjects learned which of two outcomes would occur on each trial after presentation of a particular combination of cues. Ten minutes of anodal, but not cathodal, stimulation improved implicit learning only when the left PFC was stimulated. Our results show that implicit PLC can be modified by weak anodal tDCS, which probably increases neural excitability, as has been shown in the motor and visual cortices previously. Our results suggest that further studies on the facilitation of learning and memory processes by tDCS are warranted.

Individuals with ADHD struggle with time perception. The ventromedial prefrontal cortex (vmPFC) and dorsolateral prefrontal cortex (dlPFC) are two distinct cortical areas that are involved in the psychopathology of ADHD, including time perception. In the present study, we aimed to explore if modulation of the excitability of these areas with non-invasive brain stimulation alters time perception in ADHD. Twenty-six children with ADHD performed time discrimination and time estimation/reproduction tasks in five sessions with one week interval and specific tDCS conditions. The tDCS conditions were anodal left dlPFC/cathodal right vmPFC, the reversed electrode positioning, isolated anodal left dlPFC, right vmPFC stimulation with extracranial return electrodes, and sham stimulation. An improved time discrimination was observed in all real stimulation conditions compared to sham stimulation, however the results did not differ between real stimulation conditions. For the time reproduction/estimation task, anodal vmPFC/cathodal dlPFC, isolated anodal dlPFC stimulation and isolated anodal vmPFC stimulation with extracranial return electrodes improved time reproduction, but not estimation, compared to sham stimulation. These results imply that the left dlPFC and right vmPFC are involved in time estimation, whereas the right vmPFC might be more critical for time reproduction. This finding is discussed in light of task and stimulus properties. [ABSTRACT FROM AUTHOR]

Transcranial alternating current stimulation (tACS) offers a unique method to temporarily manipulate the activity of the stimulated brain region in a frequency-dependent manner. However, it is not clear if repetitive modulation of ongoing oscillatory activity with tACS over multiple days can induce changes in grey matter resting-state functional connectivity and white matter structural integrity. The current study addresses this question by applying multiple-session theta band stimulation on the left dorsolateral prefrontal cortex (L-DLPFC) during arithmetic training. Fifty healthy participants (25 males and 25 females) were randomly assigned to the experimental and sham groups, half of the participants received individually adjusted theta band tACS, and half received sham stimulation. Resting-state functional magnetic resonance (rs-fMRI) and diffusion-weighted imaging (DWI) data were collected before and after 3 days of tACS-supported procedural learning training. Resting-state network analysis showed a significant increase in connectivity for the frontoparietal network (FPN) with the precuneus cortex. Seed-based analysis with a seed defined at the primary stimulation site showed an increase in connectivity with the precuneus cortex, posterior cingulate cortex (PCC), and lateral occipital cortex. There were no effects on the structural integrity of white matter tracts as measured by fractional anisotropy, and on behavioral measures. In conclusion, the study suggests that multi-session task-associated tACS can produce significant changes in resting-state functional connectivity; however, changes in functional connectivity do not necessarily translate to changes in white matter structure or behavioral performance. [ABSTRACT FROM AUTHOR]

Intro: Aggressive behavior represents a significant public health issue, with relevant social, political, and security implications. Non-invasive brain stimulation (NIBS) techniques may modulate aggressive behavior through stimulation of the prefrontal cortex. Aims: To review research on the effectiveness of NIBS to alter aggression, discuss the main findings and potential limitations, consider the specifics of the techniques and protocols employed, and discuss clinical implications. Methods: A systematic review of the literature available in the PubMed database was carried out, and 17 randomized sham-controlled studies investigating the effectiveness of NIBS techniques on aggression were included. Exclusion criteria included reviews, meta-analyses, and articles not referring to the subject of interest or not addressing cognitive and emotional modulation aims. Conclusions: The reviewed data provide promising evidence for the beneficial effects of tDCS, conventional rTMS, and cTBS on aggression in healthy adults, forensic, and clinical samples. The specific stimulation target is a key factor for the success of stimulation on aggression modulation. rTMS and cTBS showed opposite effects on aggression compared with tDCS. However, due to the heterogeneity of stimulation protocols, experimental designs, and samples, we cannot exclude other factors that may play a confounding role. [ABSTRACT FROM AUTHOR]

Pareidolia refers to the perception of ambiguous sensory patterns as carrying a specific meaning. In its most common form, pareidolia involves human-like facial features, where random objects or patterns are illusionary recognized as faces. The current study investigated the neurophysiological correlates of face pareidolia via transcranial alternating current stimulation (tACS). tACS was delivered at gamma (40 Hz) frequency over critical nodes of the "face perception" network (i.e., right lateral occipito-temporal and left prefrontal cortex) of 75 healthy participants while completing four face perception tasks ('Mooney test' for faces, 'Toast test', 'Noise pareidolia test', 'Pareidolia task') and an object perception task ('Mooney test' for objects). In this single-blind, sham-controlled between-subjects study, participants received 35 min of either Sham, Online, (40Hz-tACS_ON), or Offline (40Hz-tACS_PRE) stimulation. Results showed that face pareidolia was causally enhanced by 40Hz-tACS_PRE in the Mooney test for faces in which, as compared to sham, participants more often misperceived scrambled stimuli as faces. In addition, as compared to sham, participants receiving 40Hz-tACS_PRE showed similar reaction times (RTs) when perceiving illusory faces and correctly recognizing noise stimuli in the Toast test, thus not exhibiting hesitancy in identifying faces where there were none. Also, 40Hz-tACS_ON induced slower rejections of face pareidolia responses in the Noise pareidolia test. The current study indicates that 40 Hz tACS can enhance pareidolic illusions in healthy individuals and, thus, that high frequency (i.e., gamma band) oscillations are critical in forming coherent and meaningful visual perception. [ABSTRACT FROM AUTHOR]

Knowledge about the relevance of the left inferior frontal gyrus (lIFG) and the left posterior superior temporal gyrus (lpSTG) in visual recognition of word categories is limited at present. tDCS is a non‐invasive brain stimulation method that alters cortical activity and excitability, and thus might be a useful tool for delineating the specific impact of both areas on word recognition. The objective of this study was to explore whether the visual recognition process of verb categories is improved by a single tDCS session. lIFG and lpSTG areas were separately modulated by anodal tDCS to evaluate its effects on verbal recognition. Compared to sham stimulation, motor reaction times (RTs) were reduced after anodal tDCS over the lpSTG, and this effect was independent of the performing hand (right/left). These findings suggest that this region is involved in visual word recognition independently from the performing hand. The involvement of the left inferior frontal (lIFG) and posterior superior temporal (lpSTG) gyrus as typical language areas in verb recognition is uncertain. We explore the specific contribution of these areas to verb recognition via tDCS. Reaction times were reduced after anodal, but not sham, tDCS over the lpSTG. These findings reveal for the first time that lpSTG neuromodulation improves verb recognition. [ABSTRACT FROM AUTHOR]

Objective: Individuals with ADHD have deficits in reward processing and related cognitive tasks such as delay discounting and risky decision-making. The ventromedial prefrontal cortex (vmPFC) and dorsolateral prefrontal cortex (dlPFC) are two distinct cortical areas that are involved in reward processing. Methods: Twenty children with ADHD received transcranial direct current stimulation (tDCS) in three separate sessions with one of three montages each, including anodal/cathodal tDCS over the left dlPFC and right vmPFC respectively, the reversed montage, and a sham stimulation condition. During stimulation, in each session, participants performed the balloon analogue risk taking and chocolate delay discounting tasks. Results: A significant effect of stimulation condition on emotional processing was observed. Specifically, anodal tDCS over the right vmPFC, coupled with cathodal tDCS over the left dlPFC, reduced risky decision-making and delay discounting. Conclusion: These results imply that the left dlPFC and right vmPFC are involved in reward processing in children with ADHD. This finding is discussed in the light of the delay aversion theory of ADHD. [ABSTRACT FROM AUTHOR]

Background: Gait problems are an important symptom in Parkinson's disease (PD), a progressive neurodegenerative disease. Transcranial direct current stimulation (tDCS) is a neuromodulatory intervention that can modulate cortical excitability of the gait-related regions. Despite an increasing number of gait-related tDCS studies in PD, the efficacy of this technique for improving gait has not been systematically investigated yet. Here, we aimed to systematically explore the effects of tDCS on gait in PD, based on available experimental studies. Methods: Using the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) approach, PubMed, Web of Science, Scopus, and PEDro databases were searched for randomized clinical trials assessing the effect of tDCS on gait in patients with PD. Results: Eighteen studies were included in this systematic review. Overall, tDCS targeting the motor cortex and supplementary motor area bilaterally seems to be promising for gait rehabilitation in PD. Studies of tDCS targeting the dorosolateral prefrontal cortex or cerebellum showed more heterogeneous results. More studies are needed to systematically compare the efficacy of different tDCS protocols, including protocols applying tDCS alone and/or in combination with conventional gait rehabilitation treatment in PD. Conclusions: tDCS is a promising intervention approach to improving gait in PD. Anodal tDCS over the motor areas has shown a positive effect on gait, but stimulation of other areas is less promising. However, the heterogeneities of methods and results have made it difficult to draw firm conclusions. Therefore, systematic explorations of tDCS protocols are required to optimize the efficacy. [ABSTRACT FROM AUTHOR]

Neural oscillations in the cerebral cortex are associated with a range of cognitive processes and neuropsychiatric disorders. However, non-invasively modulating oscillatory activity remains technically challenging, due to limited strength, duration, or non-synchronization of stimulation waveforms with endogenous rhythms. We hypothesized that applying controllable phase-synchronized repetitive transcranial magnetic stimulation pulses (rTMS) with alternating currents (tACS) may induce and stabilize neuro-oscillatory resting-state activity at targeted frequencies. Using a novel circuit to precisely synchronize rTMS pulses with phase of tACS, we empirically tested whether combined, 10-Hz prefrontal bilateral stimulation could induce and stabilize 10-Hz oscillations in the bilateral prefrontal cortex (PFC). 25 healthy participants took part in a repeated-measures design. Whole-brain resting-state EEG in eyes-open (EO) and eyes-closed (EC) was recorded before (baseline), immediately (1-min), and 15- and 30-min after stimulation. Bilateral, phase-synchronized rTMS aligned to the positive tACS peak was compared with rTMS at tACS trough, with bilateral tACS or rTMS on its own, and to sham. 10-Hz resting-state PFC power increased significantly with peak-synchronized rTMS + tACS (EO: 44.64%, EC: 46.30%, p < 0.05) compared to each stimulation protocol on its own, and sham, with effects spanning between prefrontal and parietal regions and sustaining throughout 30-min. No effects were observed with the sham protocol. Moreover, rTMS timed to the negative tACS trough did not induce local or global changes in oscillations. Phase-synchronizing rTMS with tACS may be a viable approach for inducing and stabilizing neuro-oscillatory activity, particularly in scenarios where endogenous oscillatory tone is attenuated, such as disorders of consciousness or major depression. • Non-invasively inducing and stabilizing neural oscillations remains challenging. • We develop a controllable phase-synchronized circuit to combine rTMS and tACS. • This circuit was tested for inducing 10 Hz oscillations in healthy prefrontal cortex. • 10 Hz rTMS synchronized to the positive 10 Hz tACS peak induced stable after-effects. • Phase-synchronized stimulation is a viable approach for oscillatory neuromodulation. [ABSTRACT FROM AUTHOR]

Objective: This study examined effects of transcranial direct current stimulation (tDCS) over the dorsolateral prefrontal cortex (DLPFC) and orbitofrontal cortex (OFC) on major executive functions (EFs), including response inhibition, executive control, working memory (WM), and cognitive flexibility/task switching in ADHD. Method: ADHD children received (a) left anodal/right cathodal DLPFC tDCS and (b) sham stimulation in Experiment 1 and (a) left anodal DLPFC/right cathodal OFC tDCS, (b) left cathodal DLPFC/right anodal OFC tDCS, and (c) sham stimulation in Experiment 2. The current intensity was 1 mA for 15 min with a 72-hr interval between sessions. Participants underwent Go/No-Go task, N-back test, Wisconsin Card Sorting Test (WCST), and Stroop task after each tDCS condition. Results: Anodal left DLPFC tDCS most clearly affected executive control functions (e.g., WM, interference inhibition), while cathodal left DLPFC tDCS improved inhibitory control. Cognitive flexibility/task switching benefited from combined DLPFC-OFC, but not DLPFC stimulation alone. Conclusion: Task-specific stimulation protocols can improve EFs in ADHD. [ABSTRACT FROM AUTHOR]

Background: Application of repetitive transcranial magnetic stimulation (rTMS) for treating obsessive-compulsive disorder (OCD) has been promising and approved by the Food and Drug Administration in 2018, but effects differ between patients. Knowledge about clinical predictors of rTMS response may help to increase clinical efficacy but is not available so far. Methods: In a retrospective study, we investigated the efficacy of rTMS over the dorsolateral prefrontal cortex (DLPFC) or supplementary motor area (SMA) in 65 pharmaco-resistant OCD outpatients recruited for rTMS treatment from July 2015 to May 2017. Patients received either SMA rTMS (n = 38) or bilateral DLPFC rTMS (n = 27) in case of reporting higher affective and depressive symptoms in addition to the primary OCD symptoms. OCD symptoms and depression/anxiety states were measured at baseline (before the 1st session) and after the 20th session of rTMS. Additionally, we performed a binary logistic regression analysis on the demographic and clinical variables based on the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) 3-factor and 2-factor models and individual items to investigate potential predictors of rTMS response. Results: Patients' scores in Y-BOCS and Beck anxiety/depression inventories were significantly decreased following rTMS treatment. 46.2% of all patients responded to rTMS, based on the criterion of at least a 30% reduction in Y-BOCS scores. There was no significant difference between response rates of patients in DLPFC and SMA groups. No significant demographic predictors of rTMS efficacy were identified. The factors "obsession severity", "resistance" and "disturbance" and the "interference due to obsessions" and "resistance against compulsions" items of the Y-BOCS significantly predicted response to rTMS. Conclusions: In patients with less intrusive/interfering thoughts, and low scores in the "obsession severity", "disturbance", and "resistance" factors, rTMS might have superior effects. Identifying clinical and non-clinical predictors of response is relevant to personalize and adapt rTMS protocols in pharmaco-resistant OCD patients. Interpretation of rTMS efficacy should be done with caution due to the lack of a sham intervention condition. [ABSTRACT FROM AUTHOR]

Spatial reasoning is essential for an agent's navigation and the cognitive processing of abstract arrangements. Meta-analyses of neuroimaging data reveal that both the right posterior parietal cortex and left dorsolateral prefrontal cortex (PPC and DLPFC, respectively) show increased activation during spatial relational reasoning. To investigate whether participants' reasoning performance can be modified and potentially enhanced, anodal transcranial direct current stimulation (tDCS) was applied over either region. 51 healthy adult participants solved spatial reasoning problems after the application of either anodal tDCS over the right PPC, the left DLPFC or a sham stimulation. We expect anodal stimulation to enhance cortical excitability which would be reflected by enhanced reasoning performance in participants receiving stimulation. The results demonstrate that anodal stimulation applied over the right PPC enhances participants' performance in indeterminate reasoning problems, compared to sham and anodal stimulation over the left DLPFC. This finding is highly relevant for clarifying the cognitive mechanisms of relational reasoning and for clinical applications, e.g., enhancing or restoring higher cognitive functions for spatial representation and reasoning. [ABSTRACT FROM AUTHOR]

Transcranial direct current stimulation (tDCS) can alter cortical excitability, neural plasticity, and cognitive‐behavioral performance; however, its effects are known to vary across studies. A partial account of this variability relates to individual differences in dopamine function. Indeed, dopaminergic manipulations alter the physiological and cognitive‐behavioral effects of tDCS, and gene polymorphisms related to dopamine have predicted individual response to online tDCS (i.e., stimulation overlapping with the critical task). Notably, the role of individual differences in dopamine has not yet been properly assessed in the effect of offline tDCS (i.e., stimulation prior to the critical task). We investigated if and how the COMT Val158Met polymorphism (rs4680) modulates the after‐effect of prefrontal tDCS on verbal working memory (WM). One hundred and thirty‐nine participants were genotyped for the COMT Val158Met polymorphism and received anodal‐over‐left, cathodal‐over‐right (AL‐CR), cathodal‐over‐left, anodal‐over‐right (CL‐AR), or sham stimulation over the dorsolateral prefrontal cortex in a between‐subjects, pretest–posttest study design. WM was assessed using the N‐back task. The results provide no evidence that the COMT polymorphism impacts the after‐effect of prefrontal tDCS on WM. Taken together with previous findings on dopamine and tDCS interactions, the results of the present study suggest that (a) indirect markers of dopamine (such as COMT) are differently related to online and offline effects of tDCS, and (b) findings from studies involving pharmacological manipulation should be generalized with caution to findings of inter‐individual differences. In sum, we argue that state (i.e., a manipulation of) and trait (i.e., baseline) differences in dopamine may exert different effects on online and offline tDCS. Individual differences in dopamine activity may impact the effects that transcranial direct current stimulation (tDCS) over prefrontal cortex has on cognition. However, in the present study we found no evidence suggesting that the effect of offline tDCS, that is stimulation prior to the critical task, is modulated by differences in the COMT polymorphism, which influences prefrontal dopamine activity. Taken together with previous findings, this suggests that dopamine may differently impact tDCS overlapping with vs. prior to the critical task. [ABSTRACT FROM AUTHOR]

Prefrontal dysfunction is a hallmark in drug addiction, yet interventions exploring modulation of prefrontal cortex function in drug addiction have not been fully investigated with regard to physiological alterations. We tested the hypothesis that non-invasive prefrontal stimulation would change neural activity in crack-cocaine addiction, investigating the effects of transcranial Direct Current Stimulation (tDCS) of Dorsolateral Prefrontal Cortex (DLPFC) induced cortical excitability modulation on the visual P3 Event Related Potentials (ERP) component under neutral and drug cue exposition in crack-cocaine addicts. Thirteen crack-cocaine users were randomly distributed to receive five applications (once a day, every other day) of bilateral (left cathodal/right anodal) tDCS (20 min, 2 mA, 35 cm²) or sham tDCS over the DLPFC. Brain activity was measured under crack-related or neutral visual-cued ERPs. There were significant differences in P3-related parameters when comparing group of stimulation (active vs. sham tDCS) and number of sessions (single vs. repetitive tDCS). After a single session of tDCS, P3 current intensity in the left DLPFC increased during neutral cues and decreased during crack-related cues. This effect was opposite to what was observed in the sham-tDCS group. In contrast, repetitive tDCS increased current density not only in the DLPFC, but also in a wider array of prefrontal areas, including presumably the frontopolar cortex (FPC) orbitofrontal cortex (OFC) and anterior cingulate cortex (ACC), when subjects were visualizing crack-related cues. Thus, single and repetitive application of tDCS can impact cognitive processing of neutral and especially crack-related visual cues in prefrontal areas, which may be of importance for treatment of crack-cocaine addiction. [ABSTRACT FROM AUTHOR]

Abstract: Major Depression Disorder (MDD) is usually accompanied by alterations of cortical activity and excitability, especially in prefrontal areas. These are reflections of a dysfunction in a distributed cortico-subcortical, bihemispheric network. Therefore it is reasonable to hypothesize that altering this pathological state with techniques of brain stimulation may offer a therapeutic target. Besides repetitive transcranial magnetic stimulation, tonic stimulation with weak direct currents (tDCS) modulates cortical excitability for hours after the end of stimulation, thus, it is a promising non-invasive therapeutic option. Early studies from the 1960s suggested some efficacy of DC stimulation to reduce symptoms in depression, but mixed results and development of psychotropic drugs resulted in an early abandonment of this technique. In the last years tDCS protocols have been optimized. Application of the newly developed stimulation protocols in patients with major depression has shown promise in few pilot studies. Further studies are needed to identify the optimal parameters of stimulation and the clinical and patient characteristics that may condition response to tDCS. [Copyright &y& Elsevier]

Recent studies have shown that repetitive transcranial magnetic stimulation (rTMS) over the premotor cortex (PM) modifies the excitability of the ipsilateral primary motor cortex (M1). Transcranial direct current stimulation (tDCS) is a new method to induce neuroplasticity in humans non-invasively. tDCS generates neuroplasticity directly in the cortical area under the electrode, but might also induce effects in distant brain areas, caused by activity modulation of interconnected areas. However, this has not yet been tested electrophysiologically. We aimed to study whether premotor tDCS can modify the excitability of the ipsilateral M1 via cortico-cortical connectivity. Sixteen subjects received cathodal and anodal tDCS of the PM and eight subjects of the dorsolateral prefrontal cortex. Premotor anodal, but not premotor cathodal or prefrontal tDCS, modified selectively short intracortical inhibition/intracortical facilitation (SICI/ICF), while motor thresholds, single test-pulse motor-evoked potential and input–output curves were stable throughout the experiments. Specifically, anodal tDCS decreased intracortical inhibition and increased paired-pulse excitability. The selective influence of premotor tDCS on intracortical excitability of the ipsilateral M1 suggests a connectivity-driven effect of tDCS on remote cortical areas. Moreover, this finding indirectly substantiates the efficacy of tDCS to modulate premotor excitability, which might be of interest for applications in diseases accompanied by pathological premotor activity. [ABSTRACT FROM AUTHOR]

Simple Summary: The magnitude, distribution, and characteristics of the electric field induced in the brain by application of transcranial electric stimulation depend on the electrode configuration used and the specific parameters of stimulation. An approach to calculate the generated electric field is the computational finite element method. This method enables simulation of the current spread and electric field strength according to the electrode configuration and stimulation parameters used. However, current approaches have several limitations, which constrain the application of tDCS in empirical research and clinical practice. In this study, we provide examples of standard model-based electric field simulations corresponding to motor, dorsolateral prefrontal, and posterior parietal cortex stimulation using twenty typical electrode configurations. Two different current flow-modeling tools were used to compare the results and determine possible differences between both procedures regarding the specificity, as well as the reliability of the estimates. The results were rather consistent between both simulations. Some modest differences of the simulated distribution and intensity of the electric fields between the results of the respective modeling approaches were identified, which might have functional significance and reveal the need to empirically validate these models. The non-availability of quantitative data about the precise electric field distribution beyond the cortical target is a common limitation of both methods, which limits the determination of the spatial specificity of the intervention. These findings help to define future directions of research that allow to exploit the full potential of standard simulation approaches in the field of non-invasive brain stimulation. Transcranial direct current stimulation (tDCS) is a non-invasive brain stimulation procedure to modulate cortical excitability and related brain functions. tDCS can effectively alter multiple brain functions in healthy humans and is suggested as a therapeutic tool in several neurological and psychiatric diseases. However, variability of results is an important limitation of this method. This variability may be due to multiple factors, including age, head and brain anatomy (including skull, skin, CSF and meninges), cognitive reserve and baseline performance level, specific task demands, as well as comorbidities in clinical settings. Different electrode montages are a further source of variability between tDCS studies. A procedure to estimate the electric field generated by specific tDCS electrode configurations, which can be helpful to adapt stimulation protocols, is the computational finite element method. This approach is useful to provide a priori modeling of the current spread and electric field intensity that will be generated according to the implemented electrode montage. Here, we present standard, non-personalized model-based electric field simulations for motor, dorsolateral prefrontal, and posterior parietal cortex stimulation according to twenty typical tDCS electrode configurations using two different current flow modeling software packages. The resulting simulated maximum intensity of the electric field, focality, and current spread were similar, but not identical, between models. The advantages and limitations of both mathematical simulations of the electric field are presented and discussed systematically, including aspects that, at present, prevent more widespread application of respective simulation approaches in the field of non-invasive brain stimulation. [ABSTRACT FROM AUTHOR]

Transcranial direct current stimulation (tDCS) and high-intensity interval training (HIIT) have been demonstrated to enhance inhibitory control and working memory (WM) performance in healthy adults. However, the potential benefits of combining these two interventions have been rarely explored and remain largely speculative. This study aimed to explore the effects of acute HIIT combined with dual-site tDCS over the dorsolateral prefrontal cortex (DLPFC, F3 and F4) on inhibitory control and WM in healthy young adults. Twenty-five healthy college students (20.5 ± 1.3 years; 11 females) were recruited to complete HIIT + tDCS, HIIT + sham-tDCS, rest + tDCS, and rest + sham-tDCS (CON) sessions in a randomized crossover design. tDCS or sham-tDCS was conducted after completing HIIT or a rest condition of the same duration. The Stroop and 2-back tasks were used to evaluate the influence of this combined intervention on cognitive tasks involving inhibitory control and WM performance in post-trials, respectively. Response times (RTs) of the Stroop task significantly improved in the HIIT + tDCS session compared to the CON session across all conditions (all p values <0.05), in the HIIT + tDCS session compared to the rest + tDCS session in the congruent and neutral conditions (all p values <0.05), in the HIIT + sham-tDCS session compared to the CON session in the congruent and neutral conditions (all p values <0.05), in the HIIT + sham-tDCS session compared to the rest + tDCS session in the congruent condition (p = 0.015). No differences were found between sessions in composite score of RT and accuracy in the Stroop task (all p values >0.05) and in the 2-back task reaction time and accuracy (all p values >0.05). We conclude that acute HIIT combined with tDCS effectively improved inhibitory control but it failed to yield cumulative benefits on inhibitory control and WM in healthy adults. These preliminary findings help to identify beneficial effects of combined interventions on cognitive performance and might guide future research with clinical populations. [ABSTRACT FROM AUTHOR]

Individuals with major depressive disorder (MDD) have deficits in emotion regulation, which plays a putative role in psychopathology. The ventromedial prefrontal cortex (vmPFC) and dorsolateral prefrontal cortex (dlPFC) are assumed to be involved in respective processes. In the present study, we aimed to explore the effect of stimulation over the dlPFC and vmPFC on emotion regulation in female with MDD. Twenty women with MDD performed the Emotional Stroop, Emotional Go/No-Go, and Emotional 1-Back tasks during transcranial direct current stimulation (tDCS) in three separate sessions with the following electrode montages: anodal dlPFC (F3)/cathodal vmPFC (Fp2), anodal vmPFC (Fp2)/cathodal dlPFC (F3), and sham stimulation. Independent of the valence of the respective stimuli, accuracy and speed of interference control, accuracy of pre-potent inhibition, and accuracy, but not speed, of working memory performance improved during anodal left dlPFC/cathodal right vmPFC stimulation. Independent of stimulation conditions, interference control was reduced for sad faces, as compared to happy and neutral faces, and working memory performance was faster for happy than for neutral and sad faces. For the impact of stimulation on specific emotional qualities, anodal left dlPFC/cathodal right vmPFC, compared to sham stimulation, led to improved interference control of sad and neutral faces in the emotional Stroop task, as shown by faster reaction times. Furthermore, in that task accuracy with respect to neutral and happy face conditions was higher during both real stimulation conditions, as compared to sham stimulation. The dlPFC is involved in emotion regulation in MDD. Emotional valence is moreover relevant for the effect of stimulation over this area on interference control in MDD. [ABSTRACT FROM AUTHOR]

• The right dorsolateral prefrontal cortex (dlPFC) has a crucial role in inhibitory control in children with ADHD. • The tDCS effect in children with ADHD in prepotent inhibition is symptom severity- dependent. • Ongoing inhibition in children with ADHD improves through tDCS independent from symptom severity. The present study aimed to assess the impact of transcranial direct current stimulation (tDCS) on different domains of inhibitory control in children with mild or severe ADHD symptoms. Twenty-four children with ADHD, in two groups with severe and mild symptoms, received anodal or sham tDCS over the right dorsolateral prefrontal cortex (dlPFC) during performing inhibitory control tasks. A significant main effect of stimulation condition was found that was limited to the circle tracing task, and the incongruent condition of the flanker task. Moreover, the main effects of stimulation condition and group were non-significant, but their interaction was significant for No-Go accuracy. The results suggest that the right dlPFC has a crucial role in ongoing inhibition in children with ADHD, and that tDCS has a partially symptom severity-dependent effect on inhibitory control. These findings are discussed in connection with severity-dependent psychopathology. [ABSTRACT FROM AUTHOR]

• Self-referential processing (SRP) is an underlying cognitive mechanism of self-esteem. • High self-esteem is associated with biased attention to self-facial pictures and self-related words. • 2 mA anodal & cathodal tDCS over vmPFC promoted self-esteem rating. • Enhanced SRP and cognitive/emotional control over self-related information may explain vmPFC contribution to self-esteem. • 2 mA cathodal tDCS showed similar anodal excitatory-enhancing effects on self-esteem. Despite growing interest in underlying cognitive mechanisms of self-esteem, its neurocognitive correlates are not fully-understood. Attention bias to self-related stimuli is an example of self-referential processing (SRP) and its association with self-esteem is not well-studied. Moreover, previous studies showed that the medial prefrontal regions are involved in SRP which might suggest its involvement in self-esteem too. We investigated attentional bias to self-related stimuli and its association with the level of self-esteem in the first study (N = 30). In the second study (N = 15), we modulated activity of the ventromedial prefrontal cortex (VMPFC), as one of the medial prefrontal regions, using transcranial direct current stimulation (tDCS) to see how it affects different domains of self-esteem. Results showed that individuals with a higher level of self-esteem have more attentional bias to their own facial pictures (compared to other-facial pictures) and self-related words (compared to self-unrelated words) suggesting an impact of self-esteem on attentional and perceptual processes. Additionally, modulating activity of the VMPFC with 2 mA anodal and cathodal tDCS was associated with significantly higher ratings of global and total self-esteem but not other self-esteem domains. Our findings provide supporting evidence of neurocognitive correlates of self-esteem indicating a biasing influence of self-esteem on attention toward "self" and suggesting self-esteem as a function of SRP at behavioural and neural levels. [ABSTRACT FROM AUTHOR]

Abstract Anodal Direct Current Stimulation (DC) over prefrontal cortex improves working memory. This study investigated the influence of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs) on prefrontal anodal DC-induced effects on spatial working memory and GAP-43 expression. Male Wistar rats well-trained in radial maze procedures received five sessions of anodal epidural DC stimulation (eDCS: 400 μA, 13 min, one daily session) over the left mPFC, or a respective sham procedure, and afterwards they received a single dose (1 mg/kg) of perampanel (PRP), an AMPARs antagonist, or vehicle 30 min before the performance of 4-h delayed task. The prefrontal cortex (PFC) and hippocampus (HPC) were removed 24-h later and GAP-43 (growth-associated protein) expression was measured by Western blot analysis. Repetitive eDCS decreased the number of errors in the 4-h post-delay performance (p < 0.05) and increased the expression of GAP-43 (p < 0.01) in the PFC when compared to sham stimulation. These behavioral and prefrontal molecular changes induced by the repetitive eDCS seem to involve AMPAR activity, because they were abolished when AMPARs were blocked by PRP (p < 0.01 and 0.05, respectively). Besides, in the HPC, changes of GAP-43 expression induced by eDCS was only seen when AMPARs were blocked by PRP. Therefore, the neuronal plasticity involving AMPARs may underlie, at least in part, the improving of spatial working memory and GAP-43 expression induced by the repetitive anodal prefrontal DC stimulation. [ABSTRACT FROM AUTHOR]